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      Autoantibodies in SLE: Specificities, Isotypes and Receptors

      review-article
      , *
      Antibodies
      MDPI
      autoantibodies, isotypes, lupus, SLE, Fc receptors

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          Abstract

          Systemic Lupus Erythematosus (SLE) is characterized by a wide spectrum of auto-antibodies which recognize several cellular components. The production of these self-reactive antibodies fluctuates during the course of the disease and the involvement of different antibody-secreting cell populations are considered highly relevant for the disease pathogenesis. These cells are developed and stimulated through different ways leading to the secretion of a variety of isotypes, affinities and idiotypes. Each of them has a particular mechanism of action binding to a specific antigen and recognized by distinct receptors. The effector responses triggered lead to a chronic tissue inflammation. DsDNA autoantibodies are the most studied as well as the first in being characterized for its pathogenic role in Lupus nephritis. However, others are of growing interest since they have been associated with other organ-specific damage, such as anti-NMDAR antibodies in neuropsychiatric clinical manifestations or anti-β2GP1 antibodies in vascular symptomatology. In this review, we describe the different auto-antibodies reported to be involved in SLE. How autoantibody isotypes and affinity-binding to their antigen might result in different pathogenic responses is also discussed.

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          Most cited references216

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          Properties of mouse and human IgG receptors and their contribution to disease models.

          Impressive advances in defining the properties of receptors for the Fc portion of immunoglobulins (FcR) have been made over the past several years. Ligand specificities were systematically analyzed for both human and mouse FcRs that revealed novel receptors for specific IgG subclasses. Expression patterns were redefined using novel specific anti-FcR mAbs that revealed major differences between human and mouse systems. The in vivo roles of IgG receptors have been addressed using specific FcR knockout mice or in mice expressing a single FcR, and have demonstrated a predominant contribution of mouse activating IgG receptors FcγRIII and FcγRIV to models of autoimmunity (eg, arthritis) and allergy (eg, anaphylaxis). Novel blocking mAbs specific for these activating IgG receptors have enabled, for the first time, the investigation of their roles in vivo in wild-type mice. In parallel, the in vivo properties of human FcRs have been reported using transgenic mice and models of inflammatory and allergic reactions, in particular those of human activating IgG receptor FcγRIIA (CD32A). Importantly, these studies led to the identification of specific cell populations responsible for the induction of various inflammatory diseases and have revealed, in particular, the unexpected contribution of neutrophils and monocytes to the induction of anaphylactic shock.
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            Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication.

            Antibodies against nuclear self-antigens are characteristic of systemic autoimmunity, although mechanisms promoting their generation and selection are unclear. Here, we report that B cells containing the Y-linked autoimmune accelerator (Yaa) locus are intrinsically biased toward nucleolar antigens because of increased expression of TLR7, a single-stranded RNA-binding innate immune receptor. The TLR7 gene is duplicated in Yaa mice because of a 4-Megabase expansion of the pseudoautosomal region. These results reveal high divergence in mouse Y chromosomes and represent a good example of gene copy number qualitatively altering a polygenic disease manifestation.
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              The pathogenesis of the antiphospholipid syndrome.

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Antibodies (Basel)
                Antibodies (Basel)
                antibodies
                Antibodies
                MDPI
                2073-4468
                04 January 2016
                March 2016
                : 5
                : 1
                : 2
                Affiliations
                Centre de Recherche sur l’Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine site Bichat, Laboratoire d’Excellence Inflamex, DHU FIRE, Paris 75018, France
                Author notes
                [* ]Correspondence: nicolas.charles@ 123456inserm.fr ; Tel.: +33-1-57-27-73-06
                Article
                antibodies-05-00002
                10.3390/antib5010002
                6698872
                31557984
                a0728a47-5e62-4886-83c2-b0f87a37aebb
                © 2016 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 September 2015
                : 11 December 2015
                Categories
                Review

                autoantibodies,isotypes,lupus,sle,fc receptors
                autoantibodies, isotypes, lupus, sle, fc receptors

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